CCD-based multi-transistor active pixel sensor array

ABSTRACT

A floating electrode is used to detect ions in close proximity to the electrode. The electrode is charge coupled to other electrodes and to other transistors to form a pixel that can be placed into an array for addressable readout. It is possible to obtain gain by accumulating charge into another electrode or onto a floating diffusion (FD) node or directly onto the column line. It is desirable to achieve both a reduction in pixel size as well as increase in signal level. To reduce pixel size, ancillary transistors may be eliminated and a charge storage node with certain activation and deactivation sequences may be used.

RELATED APPLICATIONS

This application claims the benefit of priority to previously filed U.S.provisional patent application Ser. No. 61/360,493 filed Jun. 30, 2010,U.S. provisional application Ser. No. 61/360,495 filed Jul. 1, 2010,U.S. provisional application Ser. No. 61/361,403 filed Jul. 3, 2010, andU.S. provisional application Ser. No. 61/365,327 filed Jul. 17, 2010,the disclosures of all of which are incorporated herein by reference intheir entireties.

BACKGROUND

Electronic devices and components have found numerous applications inchemistry and biology (more generally, “life sciences”), especially fordetection and measurement of various chemical and biological reactionsand identification, detection and measurement of various compounds. Onesuch electronic device is referred to as an ion-sensitive field effecttransistor, often denoted in the relevant literature as an “ISFET” (orpHFET). ISFETs conventionally have been explored, primarily in theacademic and research community, to facilitate measurement of thehydrogen ion concentration of a solution (commonly denoted as “pH”).

More specifically, an ISFET is an impedance transformation device thatoperates in a manner similar to that of a MOSFET (Metal OxideSemiconductor Field Effect Transistor), and is particularly configuredto selectively measure ion activity in a solution (e.g., hydrogen ionsin the solution are the “analytes”). A detailed theory of operation ofan ISFET is given in “Thirty years of ISFETOLOGY: what happened in thepast 30 years and what may happen in the next 30 years,” P. Bergveld,Sens. Actuators, 88 (2003), pp. 1-20 (“Bergveld”), which publication ishereby incorporated herein by reference in its entirety.

Details of fabricating an ISFET using a conventional CMOS (ComplementaryMetal Oxide Semiconductor) process may be found in Rothberg, et al.,U.S. Patent Publication No. 2010/0301398, Rothberg, et al., U.S. PatentPublication No. 2010/0282617, and Rothberg et al, U.S. PatentPublication 2009/0026082; these patent publications are collectivelyreferred to as “Rothberg”, and are all incorporated herein by referencein their entirety. In addition to CMOS, however, biCMOS (i.e., bipolarand CMOS) processing may also be used, such as a process that wouldinclude a PMOS FET array with bipolar structures on the periphery.Alternatively, other technologies may be employed wherein a sensingelement can be made with a three-terminal devices in which a sensed ionleads to the development of a signal that controls one of the threeterminals; such technologies may also include, for example, GaAs andcarbon nanotube technologies.

Taking a CMOS example, a P-type ISFET fabrication is based on a P-typesilicon substrate, in which an N-type well forming a transistor “body”is formed. Highly doped P-type (P+) regions S and D, constituting asource and a drain of the ISFET, are formed within the N-type well. Ahighly doped N-type (N+) region B may also be formed within the N-typewell to provide a conductive body (or “bulk”) connection to the N-typewell. An oxide layer may be disposed above the source, drain and bodyconnection regions, through which openings are made to provideelectrical connections (via electrical conductors) to these regions. Apolysilicon gate may be formed above the oxide layer at a location abovea region of the N-type well, between the source and the drain. Becauseit is disposed between the polysilicon gate and the transistor body(i.e., the N-type well), the oxide layer often is referred to as the“gate oxide.”

Like a MOSFET, the operation of an ISFET is based on the modulation ofcharge concentration (and thus channel conductance) caused by a MOS(Metal-Oxide-Semiconductor) capacitance. This capacitance is constitutedby a polysilicon gate, a gate oxide and a region of the well (e.g.,N-type well) between the source and the drain. When a negative voltageis applied across the gate and source regions, a channel is created atthe interface of the region and the gate oxide by depleting this area ofelectrons. For an N-well, the channel would be a P-channel (andvice-versa). In the case of an N-well, the P-channel would extendbetween the source and the drain, and electric current is conductedthrough the P-channel when the gate-source potential is negative enoughto attract holes from the source into the channel. The gate-sourcepotential at which the channel begins to conduct current is referred toas the transistor's threshold voltage VTH (the transistor conducts whenVGS has an absolute value greater than the threshold voltage VTH). Thesource is so named because it is the source of the charge carriers(holes for a P-channel) that flow through the channel; similarly, thedrain is where the charge carriers leave the channel.

As described in Rothberg, an ISFET may be fabricated with a floatinggate structure, formed by coupling a polysilicon gate to multiple metallayers disposed within one or more additional oxide layers disposedabove the gate oxide. The floating gate structure is so named because itis electrically isolated from other conductors associated with theISFET; namely, it is sandwiched between the gate oxide and a passivationlayer that is disposed over a metal layer (e.g., top metal layer) of thefloating gage.

As further described in Rothberg, the ISFET passivation layerconstitutes an ion-sensitive membrane that gives rise to theion-sensitivity of the device. The presence of analytes such as ions inan analyte solution (i.e., a solution containing analytes (includingions) of interest or being tested for the presence of analytes ofinterest), in contact with the passivation layer, particularly in asensitive area that may lie above the floating gate structure, altersthe electrical characteristics of the ISFET so as to modulate a currentflowing through the channel between the source and the drain of theISFET. The passivation layer may comprise any one of a variety ofdifferent materials to facilitate sensitivity to particular ions; forexample, passivation layers comprising silicon nitride or siliconoxynitride, as well as metal oxides such as silicon, aluminum ortantalum oxides, generally provide sensitivity to hydrogen ionconcentration (pH) in an analyte solution, whereas passivation layerscomprising polyvinyl chloride containing valinomycin provide sensitivityto potassium ion concentration in an analyte solution. Materialssuitable for passivation layers and sensitive to other ions such assodium, silver, iron, bromine, iodine, calcium, and nitrate, forexample, are known, and passivation layers may comprise variousmaterials (e.g., metal oxides, metal nitrides, metal oxynitrides).Regarding the chemical reactions at the analyte solution/passivationlayer interface, the surface of a given material employed for thepassivation layer of the ISFET may include chemical groups that maydonate protons to or accept protons from the analyte solution, leavingat any given time negatively charged, positively charged, and neutralsites on the surface of the passivation layer at the interface with theanalyte solution.

With respect to ion sensitivity, an electric potential difference,commonly referred to as a “surface potential,” arises at thesolid/liquid interface of the passivation layer and the analyte solutionas a function of the ion concentration in the sensitive area due to achemical reaction (e.g., usually involving the dissociation of oxidesurface groups by the ions in the analyte solution in proximity to thesensitive area). This surface potential in turn affects the thresholdvoltage of the ISFET; thus, it is the threshold voltage of the ISFETthat varies with changes in ion concentration in the analyte solution inproximity to the sensitive area. As described in Rothberg, since thethreshold voltage VTH of the ISFET is sensitive to ion concentration,the source voltage VS provides a signal that is directly related to theion concentration in the analyte solution in proximity to the sensitivearea of the ISFET.

Arrays of chemically-sensitive FETs (“chemFETs”), or more specificallyISFETs, may be used for monitoring reactions—including, for example,nucleic acid (e.g., DNA) sequencing reactions, based on monitoringanalytes present, generated or used during a reaction. More generally,arrays including large arrays of chemFETs may be employed to detect andmeasure static and/or dynamic amounts or concentrations of a variety ofanalytes (e.g., hydrogen ions, other ions, non-ionic molecules orcompounds, etc.) in a variety of chemical and/or biological processes(e.g., biological or chemical reactions, cell or tissue cultures ormonitoring, neural activity, nucleic acid sequencing, etc.) in whichvaluable information may be obtained based on such analyte measurements.Such chemFET arrays may be employed in methods that detect analytesand/or methods that monitor biological or chemical processes via changesin charge at the chemFET surface. Such use of ChemFET (or ISFET) arraysinvolves detection of analytes in solution and/or detection of change incharge bound to the chemFET surface (e.g. ISFET passivation layer).

Research concerning ISFET array fabrication is reported in thepublications “A large transistor-based sensor array chip for directextracellular imaging,” M. J. Milgrew, M. O. Riehle, and D. R. S.Cumming, Sensors and Actuators, B: Chemical, 111-112, (2005), pp.347-353, and “The development of scalable sensor arrays using standardCMOS technology,” M. J. Milgrew, P. A. Hammond, and D. R. S. Cumming,Sensors and Actuators, B: Chemical, 103, (2004), pp. 37-42, whichpublications are incorporated herein by reference and collectivelyreferred to hereafter as “Milgrew et al.” Descriptions of fabricatingand using ChemFET or ISFET arrays for chemical detection, includingdetection of ions in connection with DNA sequencing, are contained inRothberg. More specifically, Rothberg describes using a chemFET array(in particular ISFETs) for sequencing a nucleic acid involvingincorporating known nucleotides into a plurality of identical nucleicacids in a reaction chamber in contact with or capacitively coupled tochemFET, wherein the nucleic acids are bound to a single bead in thereaction chamber, and detecting a signal at the chemFET, whereindetection of the signal indicates release of one or more hydrogen ionsresulting from incorporation of the known nucleotide triphosphate intothe synthesized nucleic acid.

However, traditionally, ion concentration in the analyte solution ismeasured by measuring an instantaneous voltage at an output of theISFET. The signal-to-noise ratio provided by the instantaneous voltagemay not be as high as desired in a lot of situations. Further, with thescaling of ISFET sensor array designs, more ISFET sensors are packed ona chip. Thus, there is a need in the art to provide a better SNR thanthe instantaneous voltage measurement and also a need for on-chip datacompression.

Moreover, with the scaling of ISFET sensor array designs, more and moreISFET sensors are packed on a chip. Thus, there is a need in the art toprovide a readout scheme to output measured data from a chip at a highspeed.

BRIEF DESCRIPTION OF THE DRAWING FIGURES

FIG. 1 illustrates a 1T ion sensitive pixel according to an embodimentof the present invention.

FIG. 2 illustrates the cross section of a 1T pixel according to anembodiment of the present invention.

FIG. 3 shows the schematic of an array of pixels with column readoutswitches according to an embodiment of the present invention.

FIG. 4 shows the source follower configuration of the 1T pixel accordingto an embodiment of the present invention.

FIG. 5A shows a 1T common source ion sensitive pixel according to anembodiment of the present invention.

FIG. 5B shows the pixel in a common source readout configurationaccording to an embodiment of the present invention.

FIG. 5C shows a common source equivalent circuit according to anembodiment of the present invention.

FIG. 6 shows a schematic of an array of pixels with column readoutswitches according to an embodiment of the present invention.

FIG. 7A shows a cross section of a 1T common source pixel according toan embodiment of the present invention.

FIG. 7B shows a cross section of a 1T common source pixel according toan embodiment of the present invention.

FIG. 8 shows a common source pixel with a cascoded row selection deviceaccording to an embodiment of the present invention.

FIG. 9 shows a one-transistor pixel array with cascoded column circuitaccording to an embodiment of the present invention.

FIGS. 10A and 10B show a one-transistor pixel array according to anembodiment of the present invention.

FIG. 11 shows a two-transistor (2T) pixel according to an embodiment ofthe present invention.

FIG. 12A to 12H illustrate 2T pixel configurations according toembodiments of the present invention.

FIG. 13A to 13D illustrate common source 2T cell configurationsaccording to embodiments of the present invention.

FIG. 14A shows a 2T pixel array according to an embodiment of thepresent invention.

FIGS. 14B and 14C show a layout for a 2×2 2T pixel array according to anembodiment of the present invention.

FIG. 15 shows a capacitive charge pump according to an embodiment of thepresent invention.

FIG. 16 shows a charge pump according to an embodiment of the presentinvention.

FIG. 17 shows a charge pump according to an embodiment of the presentinvention.

FIG. 18 shows a charge pump according to an embodiment of the presentinvention.

FIG. 19 shows a basic IS accumulation pixel according to an embodimentof the present invention.

FIG. 20A-Q show surface potential diagrams for basic charge accumulationaccording to an embodiment of the present invention.

FIGS. 21 and 22 show an IS accumulation pixel with 2 transistorsaccording to an embodiment of the present invention.

FIG. 23 shows surface potential diagrams for the pixel of FIG. 22according to an embodiment of the present invention.

FIG. 24 shows an IS accumulation pixel with 2 transistors and 4electrodes according to an embodiment of the present invention.

FIG. 25 shows the surface potential diagrams for the pixel of FIG. 24according to an embodiment of the present invention.

FIG. 26 shows an IS accumulation pixel with 1 transistor and 3electrodes according to an embodiment of the present invention.

FIG. 27 shows a three transistor (3T) active pixel sensor according toan embodiment of the present invention.

FIG. 28 shows an alternate embodiment of a 3T active pixel sensor.

FIG. 29 shows a 3T active pixel sensor with a sample and hold circuitaccording to an embodiment of the present invention.

FIG. 30 shows a 3T active pixel sensor with a correlated double samplingcircuit according to an embodiment of the present invention.

FIG. 31 shows a 2.5T active pixel sensor array according to anembodiment of the present invention.

FIG. 32 shows a 1.75T active pixel sensor array according to anembodiment of the present invention.

DETAILED DESCRIPTION One-Transistor Pixel Array

A floating gate (FG) transistor may be used to detect ions in closeproximity to the gate electrode. The transistor may be configured withother transistors to form a pixel that can be placed into an array foraddressable readout. In the simplest form, the ancillary transistors areused solely to isolate and select the floating gate transistor forreadout in an array. The floating gate transistor may be achemically-sensitive transistor, and more specifically, achemically-sensitive field effect transistor (ChemFET). The ChemFET maybe designed with a metal-oxide-semiconductor field-effect transistor(MOSFET) containing self-aligned source and drain implants fabricatedusing standard complementary metal-oxide-semiconductor (CMOS)processing. The ChemFET may be an ion sensitive FET (ISFET), and may bea PMOS or an NMOS device.

To reduce the pixel size to the smallest dimensions and simplest form ofoperation, the ancillary transistors may be eliminated to form an ionsensitive field-effect transistor (ISFET) using one transistor. Thisone-transistor, or 1T, pixel can provide gain by converting the draincurrent to voltage in the column. Parasitic overlap capacitance betweenterminals of the transistor limits the gain. The capacitance ratios alsoallow consistent pixel-to-pixel gain matching and relatively constantcurrent operation which justifies the use of a row selection line whichcan sink the necessary current without causing unacceptable variation.Derivatives of this allow for increased programmable gain through acascoded transistor enabled during readout. Configurable pixels can becreated to allow both common source read out as well as source followerread out.

FIG. 1 illustrates a 1T ion sensitive pixel according to one embodimentof the present invention. As shown, the pixel 100 may have one and onlyone transistor 101, one and only one row line R and one and only onecolumn line C. The transistor 101 is shown as an n-channel MOSFET (NMOS)transistor in a p-type epitaxial substrate available using standard CMOSprocesses in this embodiment. It should be understood that NMOS is onlyused as an example in the present invention, and the transistor 101 maybe a PMOS as well. The selection of NMOS or PMOS as a preferred devicedepends on which device does not require a top-side bulk contact for agiven process. Typically NMOS is preferred when using a P+ wafer with P−epitaxy layer (called an epi-wafer) because the underlying P+ substratebiases the bulk on an array of pixels without the need to wire in a bulkcontact at each pixel location. Therefore, a global bulk contact is anattractive combination for use with a 1T pixel where a small pixel pitchis required. The floating gate G of the transistor 101 may containtrapped charge, which may be properly discharged such that the electrodeis at approximately the same potential as the substrate when all otherterminals are also biased to the substrate potential. The row line R maybe capacitively coupled to the drain D of the transistor 101, and thecolumn line may be coupled to the source S of the transistor 101. A gateto drain overlap capacitance Cgd may form between the gate G and thedrain D. The pixel 100 may be addressable from the row line R, whichsupplies the column current (i.e., drain-to-source current of thetransistor 101) and boosts the potential at the floating gate.

In a one-transistor pixel array, such as the one shown in FIG. 3, rowselection may be facilitated by boosting the FG nodes for a particularrow. In one embodiment, the readout of the pixel is a winner-take-allcircuit, which will be described below.

FIG. 2 illustrates the cross section of a 1T pixel according to oneembodiment of the present invention. The transistor in the 1T pixel maybe formed using an n-channel FET device by having a drain D and a sourceS formed using n-type implants within a p-type semiconductor. As shown,the transistor may have a floating gate G, the drain D and the source S.The source S may be coupled to the column line C and the drain D may becoupled to the row line R. Lightly doped drain (LDD) regions may createa gate to drain overlap capacitance Cgd and/or a gate to source overlapcapacitance Cgs.

In one embodiment, the 1T ion pixel 100 may work by boot-strapping therow selection line R to the floating gate G while at the same timeproviding a source of current for the column line bias. In the simplestform, this bootstrapping occurs without adding any extra capacitors. Thegate to drain overlap capacitance Cgd, as shown in FIGS. 1 and 2, maynaturally form the necessary capacitive coupling. To increase capacitivecoupling, if desired, the row selection metal line can form an extrametal capacitor to the floating metal electrode or more significantsource and drain extensions can be made with ion implantation.

FIG. 3 shows the schematic of an array of pixels with column readoutswitches according to one embodiment of the present invention. Forillustrative purposes, four 1T pixels 301, 302, 303 and 304 of an array300 are shown arranged into two rows and two columns, though the array300 could extend to an array of any size of 1T pixels. The 1T pixel maybe similar to the one shown in FIG. 1. The drains of pixels 301 and 302are coupled to a row line R0, and the sources of pixels 301 and 302 arecoupled to column lines C0 and C1 respectively. The drains of pixels 303and 304 are coupled to a row line R1, and the sources of pixels 303 and304 are coupled to column lines C0 and C1 respectively. The pixel arraycan be loaded with a current source but the simplest implementationmakes use of just a single switch that precharges the column line to alow potential such as the substrate potential. A column readout switch305 is coupled to the column line C0 and a column readout switch 306 iscoupled to the column line C1. The column readout switch 305 comprises aswitch Sa, a switch Sb, a current source Isource and a capacitor Cw. Theswitch Sa is used for precharging the column line and to initialize thecolumn line quickly between samples. The switch Sb is used to sample andhold the analog value that is read on the column line. In some cases,neither a sampling capacitor nor a switch Sb are required if the pixelis converted to digital through and analog to digital converter whilethe pixel is held under bias. The switch Sa is used to ground the columnline C0. After the column line switch Sb is open the sample is held inthe capacitor, the final value on the column line, as sampled by thecapacitor, will be determined almost entirely by the active row becausethe circuit operates according to “a winner take-all” mode (i.e., theresulting voltage represents the largest voltage of the ISFETs coupledto the readout circuit). The column readout circuit 306 functionssimilarly.

The operation of this pixel depends on the fact that the signal range ofany given pixel is small compared to the supply voltage or read range ofthe source follower. For example, the useful signal range may be only100 mV and the supply voltage may be 3.3V. When a row is selected, the Rline is driven to an active high voltage VH, while all other row linesare held at an active low voltage VL. The voltage VL is selected to beapproximately equal to the nominal voltage on the column line C duringthe readout of any given pixel. Because the signal range is small, thisvoltage is known to within 100 mV in this example. Therefore, the drainto source voltage of all inactive pixels is always held to small values.This point is only critical if the gate to source voltage of inactivepixels is near the threshold of the device. For the row driven to VH,the FG voltages for that row are significantly higher than the otherrows because of the bootstrapping that occurs when the row linetransitions to VH. After the column line switch Sb is open, the finalvalue on the column line will be determined almost entirely by theactive row because the circuit operates according to the winner take-allmode.

There are two sources of current from other rows that can distort thesignal value (one that adds current and one that takes away current) andthere must be enough bootstrapping available to successfully read pixelswithout significant interaction from the other rows that produce thesesources. The analysis to determine how much bootstrapping is needed isas follows. By the time the pixel is sampled, the device has entered thesubthreshold region of operation which has a transconductance slope, forexample, of approximately 100 mV/decade. This means that for every 100mV of change in gate voltage, the current changes by 10 times. In orderto effectively read a single pixel, a criteria is set so that 99% of thecurrent on the column line is attributable to the active row and only 1%is attributable to the inactive rows (distortion current). From here itcan be determined how much bootstrapping is necessary. With only 2 rowsin the pixel array, a 200 mV difference in the floating gate voltages isneeded according to the subthreshold slope. Since a signal range ofabout 100 mV is also needed to be accounted for, the total requirementis about 300 mV. If there are 10 rows, there may be 10 times morecontribution from inactive rows. Therefore an extra 100 mV is needed. Ifthe array is increased to 100 rows, another 100 mV is needed. If thearray is increased to 10^n rows, 300+100*n mV is needed. As an example,a 10000 (10^4) row pixel array only requires a total of 700 mV(300+100*4) of bootstrapping. This amount of bootstrapping can beachieved from the overlap capacitance of the gate and drain. If morecapacitance is needed, extra coupling can be facilitated in the masklayout. The above analysis only applies to pixels contributing to thereadout current.

Pixels can also take current away from the column line and sink itthrough the deactivated row lines. Since the deactivated row line is setto approximately the level of the column line, this current draw will beminimal but it must still be quantified and controlled. To accomplishthis, the final current on the column line should not be allowed todiminish beyond a certain level. This is ensured by loading the columnwith a small current sink such as 1 uA. For a W/L (width to length)ratio of 1, a transistor biased at its threshold will have a saturationcurrent of about 0.1 uA. This current decreases by a factor of 10 forevery 100 mV of reduction in gate to source voltage. If less than 1%contribution of current is required, the VGS of inactive pixels needs tobe kept to 100+100*n mV below the threshold voltage where 10^n is thenumber of pixels in the row. Thus, for a 10000 row pixel array, VGSneeds to be kept to 500 mV below threshold. A typical 3.3V NMOStransistor has a VT of 600 mV. Therefore, VGS should be less than 100 mVfor inactive pixels. Assuming that the FG has a nominal voltage of 0Vwhen the row (R) and column (C) lines are at 0V, this condition is meteven as R and C couple to the FG. If the FG has a larger nominal voltagethan 0V (for example, due to the trapped charge), more bootstrapping isnecessary to cause the column line to reach a level within 100 mV of theFG. As long as the nominal FG voltage is sufficiently low, the secondcriteria for minimizing distortion current is not a limiting factor.Finally, enough bootstrapping is needed to produce a current on thecolumn line that matches the bleeding current so that the pixel canproduce a measurable voltage on the column line. If VG is nominally 0 v,then 700 mV is needed for bootstrapping. Therefore, for an NMOS with VTas large as 600 mV, the amount of bootstrapping required is simplylimited by the VT. In order to readout the pixel with margin, a goodtarget for bootstrapping is 1V. This leaves 300 mV of range forvariation. Achieving 1V of bootstrapping is practical within a 3.3Vsupply.

All the current from the column readout is distributed through the rowline. This causes significant droop in the voltage of the row line ifthe column current is also significant. The voltage droop affects thebootstrapping level but is not detrimental to the readout of the sourcefollower because variation in drain voltage has only a second ordereffect. Since pixels are read out with multiple samples, offsets arecanceled such that the droop does not affect the sensitivity of thepixels.

It should be noted that the same layout can be used for both sourcefollower readout and common source readout as long as optimizations arenot made for either. Only accommodations that need to be made are in thecolumn circuits. This makes for a flexible readout architecture andeither readout method may be used depending on the necessary signalrange. If the signal needs a high gain, the common source mode should beused. Otherwise, the source follower mode may be used.

FIG. 4 shows the source follower configuration of the 1T pixel accordingto one embodiment of the present invention. The source follower mode hasa buffered readout and operates in a voltage mode, and has a gain lessthan 1. As shown, the sole transistor 401 may be coupled to an inputvoltage V1 at its gate G and to a fixed voltage at its drain D. Thesource S of the transistor 401 may be grounded via a current sourceIsource. The output voltage Vo may be taken from the source of thetransistor 401. A coupling capacitance Cc may exist between the inputand the gate of the transistor 401, a parasitic capacitor Cgd may existbetween the gate G and the drain D of the transistor 401, and aparasitic capacitor Cgs may exist between the gate and the source S ofthe transistor 401.

The following analysis is given for the gain of the source followerreadout. Referring to FIG. 4, the gain of the circuit (G) may be definedas Vo/Vi. Using reference pixels the electrode of the system may beswept to measure the gain such that Vo/Vi=G. Using the measured value ofa parameter G, which is 0.65 in this example, the ratio of Cc to Cgd maybe determined. As will be discussed later, it is this ratio that willdetermine the gain in the common source mode. The input capacitance ofthe source follower is Ci=Cgd+Cgs(I−Asf), wherein Asf is the gain ofsource follower. Due to the body effect, Asf is approximately 0.85. Thecapacitive divider relating to the input voltage on the FET isCc/(Ci+Cc) and therefore, Cc/(Ci+Cc)=G/Asf. Since Cgs is about 3-5 timeslarger than Cgd and Asf is about 0.85, Ci is approximately 2Cgd.Therefore, Cc=2Cgd(G/(Asf−G)). In this example, the ratio of Cc to Cgdis about 6.5.

In one embodiment, the present invention obtains voltage gain by readingout with the common source configuration. It is desirable to achieveboth a reduction in pixel size as well as an increase in signal level.The present invention eliminates the ancillary transistors in otherpixel designs (e.g., 2T and 3T discussed below) and uses the source ofthe ISFET as the selection line to achieve both of these goals. Thecommon source mode is a gain mode and a current mode.

FIG. 5A shows a 1T common source ion sensitive pixel according to oneembodiment of the present invention. As shown, the pixel 500 may haveone and only one transistor 501, one and only one row line R and one andonly one column line C. The transistor 501 is shown as an n-channelMOSFET (NMOS) transistor in a p-type epitaxial substrate available usingstandard CMOS processes in this embodiment, although it may be ap-channel MOSFET as well. An NMOS device is typically preferred in usewith a P+ epi wafer that requires no front side bulk contacts.Technically a PMOS could be use with a N+ epi wafer, but thisconfiguration is not as commonly produced in standard CMOS processes.The row line R may be coupled to the source S of the transistor 501, andthe column line may be coupled to the drain D of the transistor 501. Therow selection is facilitated by switching on a path for the sourcevoltage, and the readout of the pixel is through the drain.

The schematic of an array of pixels with column readout switchesaccording to one embodiment of the present invention is shown in FIG. 6.The array 600 has four 1T common source pixels 601, 602, 603 and 604.The 1T pixel may be similar to the one shown in FIG. 5A. In thisexample, pixels are arranged into two rows and two columns. The drainsof pixels 601 and 602 are coupled to a column line C0, and the sourcesof pixels 601 and 602 are coupled to row lines R0 and R1 respectively.The drains of pixels 603 and 604 are coupled to a column line C1, andthe sources of pixels 603 and 604 are coupled to row lines R0 and R1respectively. A column readout switch 605 is coupled to the column lineC0 and a column readout switch 606 is coupled to the column line C1. Thecolumn readout switch 605 comprises a switch Sa, a switch Sb, a resistorR and a capacitor C_(w0). The column readout switch 606 comprises aswitch Sa, a switch Sb, a resistor R and a capacitor C_(w1). The switchSa may pull the voltage on the column line to a fixed voltage, forexample, to a 3.3V supply. When the column line switch Sb is open, thefinal value on the column line will be determined by the active rowsince the switch Sb, along with the capacitor C_(w0), acts as a sampleand hold circuit.

The pixel array can be loaded with a current source with finite outputresistance or another load device such as a resistor. Normally the rowselection lines will be held at an active high voltage VH. When a row isselected for readout, its row selection line is pulled low to VL. Thevalue of VL is set such that the nominal current level is about 1 uA. Ifthe FG has a value of 100 mV higher than the norm, 10 times this currentwill result on the column line. If the value of FG is 100 mV lower thanthe norm, the current will be 10 times lower. The settling time of thesignal on the column line will be signal dependent. The voltage gain isachieved with the selection of the value of R and it can be configurableto achieve programmable gain. For example, if R is 100 k ohms, then the100 mV, translates to 1V at the output.

The actual circuit is more complicated than just a simple common sourceamplifier because of the parasitic capacitance involved. Since the FGnode is not driven, but rather capacitively coupled to the output, thereis a feedback mechanism that limits the gain. This limit is roughlyequal to the total capacitance at the FG node to the gate to draincapacitance. This ratio may be about 3. It could be designed to achievehigher gain such as 10 times with careful mask operations to reducesource and drain extensions.

FIG. 7A shows the cross section of a 1T common source pixel according toone embodiment of the present invention. The transistor in the 1T pixelmay be formed using an n-channel FET device by having a drain D andsource S be formed using n-type implants within a p-type semiconductor.As shown, the transistor may have a floating gate G, the drain D and thesource S. The source S may be coupled to the row line R and the drain Dmay be coupled to the column line C. Lightly doped drain (LDD) regionsmay create a gate to source overlap capacitance Cgs and a gate to drainoverlap capacitance Cgd.

The overlap capacitance created by the LDD regions can be reduced byskipping the LDD implants at the drain for the device. FIG. 7B shows thecross section of a 1T common source pixel according to one embodiment ofthe present invention. FIG. 7B shows a drain node with a missing LDDregion. This missing region reduces the capacitance and increases gain.This can be achieved through masking out the LDD implants and can beimplemented in standard CMOS processing.

In the 1T pixel shown in FIG. 5A, since the source current must besupplied from the row selection line, variations in current due tovariations in signal will create variations in voltage. These variationscan distort the measurements. Therefore the row selection line should below resistance and the driver for that line should also supply a steadysource voltage independent of the current load. Where this is notpossible, the current can be supplied from the column line and a secondselection transistor can be added to form a 2T pixel for common sourceread out, as shown in FIG. 10A described below. Since the gain islimited by the parasitic overlap capacitance, it is expected that thebest load to use is a current source implemented with transistors ofhigh output resistance. In this case, relatively constant current willbe maintained in all devices since the gain is achieved throughcapacitor ratios. This makes the 1T configuration feasible since voltagevariation at the source is minimal, even with a single row selectionline that carries all the current.

The pixel in common source readout configuration is shown in FIG. 5B.The transistor forms an amplifier with negative voltage gain. Thisnegative voltage gain forms a natural feedback loop with the parasiticcapacitors in order to control the gain. The open loop gain of theamplifier is A=gm(ro), wherein gm is a transconductance. The value A istypically larger than 100 for a given bias condition and processtechnology. As shown in FIG. 5C, the common source equivalent circuithas a feedback capacitance Cgd, a coupling capacitance Cc, and Cgs.

Since A is large compared to the loop gain, the negative input terminalmay be considered as a virtual ground node and the gain of the circuitmay be determined as Vo/Vi=−Cc/Cgd. Since this ratio is known from theanalysis or measured values of the source follower configuration, thegain may be determined to be about 6.5. However compared to the sourcefollower, the gain is Vo/Vi=2/(Asf−G). In this example, a gain of 10 isrealized over the source follower configuration. A lower bound on thisgain is given by assuming that the input capacitance of the sourcefollower is solely due to Cgd and that the Asf is equal to 1. In thiscase the gain is about 3. Since neither of these conditions isrealistic, the gain is expected to always exceed this number. Thus, ifthe gain of the source follower configuration of a pixel is known, thegain of the common source configuration of this pixel is also known. Inaddition, the higher the gain, the more sensitive the pixel is. Thismakes the common source configuration preferable.

Flicker noise can be reduced by using a channel doping of the same typeas the minority carrier. For example, an NMOS with a n-type implantproduces a buried channel transistor. To shift the workfunction of thedevice, a P+ gate electrode can be used.

One-Transistor Pixel Array with Cascoded Column Circuit

One derivative of the one-transistor pixel allows for increasedprogrammable gain through a cascoded transistor enabled during readout.

Since the gain of the common source readout is limited by the Cgdcapacitance, as shown in FIG. 5B, lowering this capacitance can increasethe gain. FIG. 8 shows a common source pixel with a cascoded rowselection device. As shown, a transistor 801 may be added to a commonsource pixel, e.g., the circuit shown in FIG. 5B. The gate of thetransistor 801 may be coupled to a voltage Vb, and the source of thetransistor 801 may be coupled to the drain of the transistor 501. Theoutput voltage Vo may be taken from the drain of the transistor 801. Thecascode effectively removes the Cgd capacitance from the feedback loopand replaces it with Cds which is much smaller. Gain on the order of theloop gain is then achievable, which may exceed 100.

Higher gain and variable gain may be produced in the 1T configuration bybringing the cascode device outside the pixel to the column line. FIG. 9shows a one-transistor pixel array with cascoded column circuit. Thisallows high gain and yet still allows the pixel pitch to be minimizedwith only 1 transistor per pixel. The shown pixel array is a columnhaving a number of one-transistor pixels (e.g., 500) connected inseries, and has a cascode device at the base of the array. The cascodedevice may comprise a transistor 901. The gate of the transistor 901 maybe coupled to a bias voltage Vb, the source of the transistor 901 may becoupled to the drain of the transistor 501, and the drain of thetransistor 901 may be coupled to a fixed voltage via a current source.The output voltage Vo may be taken from the drain of the transistor 901.It should be understood that the array may have a number of columns.

In this case, the cascode forces the drain of the pixel to remain at afairly steady voltage over the range of inputs. This causes the pixel topush nearly all of the change in current through the cascode device atthe base of the array and into the current load. This reduces thenegative feedback from Cds, which would otherwise limit the gain. Giventhat the current load has infinite output resistance and there iseffectively no coupling capacitor to the FG node, the gain of the pixelis now −(gm1rO1+1)gm2rO2, wherein gm1 is the transconductance of thecascode device at the base of the column line and gm2 is thetransconductance of the pixel and rO1 and rO2 are the small signaloutput resistances as seen at the drain. The value of the outputresistance is determined by channel length modulation. Longer gatelengths produce higher output resistance because the effect of channellength modulation is minimized. Since this gain is so large, it can belimited and configured by variation of the current source outputresistance, which is shown as Radj in FIG. 9. This allows forprogrammable gain at the column level while maintaining a simple 1transistor pixel. The gain of the pixel is then set by −gm2RL, assumingthat the load resistance RL is much smaller than the output resistanceof the cascode configuration, where R_(L) is the adjusted value of Radj.The gain is now configurable and programmable within the range of 1 to100 or larger. For example, if the bias current is about 5 uA, thetransconductance of the pixel is about 50 uA/V, and a load resistance of20K ohms is needed for gain of 1. A gain of 10 is achieved with a 200Kohm load and gain of 100 with a 2M ohm load. There are many was toimplement the effect of the cascode device at the column line. The mainpurpose of the cascode, as shown in FIG. 901 as an NMOS transistor, isthat the column line is held to a potential that is largely independentof the current level in the pixel. A differential amplifier with highgain can be applied to maintain this condition more precisely. Thisapproach would be called gain-enhanced cascoding.

Various layout choices can be made to implement a 1 T and 2T transistor.In order to reduce the size of the pixel the source and drains ofadjacent pixels can be shared. In this way a single row selection lineenables 2 rows at a time. This reduces the row wiring: two columns arethen read out at once for a given column pitch. Such a scheme is shownin FIGS. 10A and 10B. As shown, a pixel array 1000 comprises transistors1001, 1002, 1003 and 1004 in a column. The source of 1001 is coupled toa row line R2, and the source of 1004 is coupled to a row line R0.Transistors 1001 and 1002 may form a mirror M1, and transistors 1003 and1004 may form a mirror M2. The drain of 1001 and 1002 are coupled to acolumn line CA, and the drain of 1003 and 1004 are coupled to a columnline CB.

In one embodiment, the cascoded device is gain-enhanced with adifferential amplifier in feedback to control a transistor thatmaintains a constant voltage on the column line.

Two-Transistor Pixel Array

In a pixel array, a row selection device may be used for selection andisolation. When a row selection line is activated, the row selectiondevice (a MOSFET) forms a channel due to the gate voltage exceeding athreshold voltage and acts like a switch. When the row selection isdeactivated, the channel is diminished. It is important to note that arow selection device never really completely turns “on” or “off”. Itonly approximates a switch. When the gate is substantially lower thanthe source of the row selection transistor, good isolation is achievedand the pixel with the active row selection can be read effectivelywithout input from deactivated pixels. With many rows in an array ofpixels, it is necessary to achieve a given level of isolation for eachrow selection device. That is, the requirements for the row selectiondevice depend on the number of rows.

FIG. 11 shows a two-transistor (2T) pixel according to one embodiment ofthe present invention. As shown, the 2T pixel 1100 comprises an ISFET1101 and a row selection device 1102. In the pixel 1100, the source ofthe ISFET 1101 is coupled to a column line Cb, the drain of the rowselection device 1102 is coupled to a column line Ct, and the drain ofthe ISFET 1101 is coupled to the source of the row selection device1102. The gate of the row selection device 1102 is coupled to a row lineR.

Both ISFET 1101 and the row selection device 1102 are shown as NMOS, butother types of transistors may be used as well. The 2T pixel 1100 isconfigured as the source follower readout mode, although 2T pixels maybe configured as the common source readout mode.

FIG. 12A to 12H illustrate more 2T pixel configurations according toembodiments of the present invention. In these Figures, “BE” stands for“with body effect”, i.e. the ISFET is body-effected because the bodyterminal is connected to the analog supply voltage or analog groundvoltage (depending on whether the ISFET transistor type is p-channel orn-channel MOS). The body effect is eliminated if the body terminal isconnected to the source terminal of the transistor. “PR” stands for“PMOS devices in reversed positions”, i.e. the positions of thep-channel ISFET and row selection device in the pixel circuit topologyhave been reversed (or switched around). “PNR” stands for “PMOS/NMOSdevices in reversed positions”, i.e. the positions of the p-channelISFET and n-channel row selection device in the pixel circuit topologyhave been reversed (or switched around).

FIG. 12A illustrates a 2T pixel, according to one embodiment of thepresent invention. As shown, both the ISFET and the row selection deviceSEL are p-channel MOS transistors, with the source terminal of the ISFETcoupled to the drain terminal of the row selection device. The drainterminal of the ISFET is connected to the analog ground voltage and thesource terminal of the row selection device is connected to a currentsource, which provides a bias current to the pixel. The output voltageVout is read out from the source terminal of the row selection device.

FIG. 12B illustrates a 2T pixel, according to one embodiment of thepresent invention. As shown, both the ISFET and the row selection deviceSEL are p-channel MOS transistors, with the source terminal of the ISFETconnected to the body terminal to eliminate the body effect, and alsoconnected to the drain terminal of the row selection device. The drainterminal of the ISFET is connected to the analog ground voltage and thesource terminal of the row selection device is connected to a currentsource, which provides a bias current to the pixel. The output voltageVout is read out from the source terminal of the row selection device.

FIG. 12C illustrates a 2T pixel, according to one embodiment of thepresent invention. As shown, both the ISFET and the row selection deviceSEL are p-channel MOS transistors, with the drain terminal of the ISFETconnected to the source terminal of the row selection device. The drainterminal of the row selection device is connected to the analog groundvoltage and the source terminal of the ISFET is connected to a currentsource. The output voltage Vout is read out from the source terminal ofthe ISFET.

FIG. 12D illustrates a 2T pixel, according to one embodiment of thepresent invention. As shown, both the ISFET and the row selection deviceSEL are p-channel MOS transistors, with the drain terminal of the ISFETconnected to the source terminal of the row selection device. The drainof the row selection terminal is connected to the analog ground voltageand the source terminal of the ISFET is connected to a current source,which provides a bias current to the pixel. The output voltage Vout isread out from the source terminal of the ISFET. The source terminal ofthe ISFET is connected to the body terminal to eliminate the bodyeffect.

FIG. 12E illustrates a 2T pixel, according to one embodiment of thepresent invention. As shown, the ISFET and the row selection device SELare p-channel and n-channel MOS transistors respectively, with theirsource terminals connected together. The drain terminal of the ISFET isconnected to the analog ground voltage and the drain of the rowselection device is connected to a current source, which provides a biascurrent to the pixel. The output voltage Vout is read out from the drainterminal of the row selection device.

FIG. 12F illustrates a 2T pixel, according to one embodiment of thepresent invention. As shown, the ISFET and the row selection device SELare p-channel and n-channel MOS transistors respectively, with theirsource terminals connected together. The drain terminal of the ISFET isconnected to the analog ground voltage and the drain of the rowselection device is connected to a current source, which provides a biascurrent to the pixel. The output voltage Vout is read out from the drainterminal of the row selection device. The source terminal of the ISFETis connected to the body terminal to eliminate the body effect.

FIG. 12G illustrates a 2T pixel, according to one embodiment of thepresent invention. As shown, the ISFET and the row selection device SELare p-channel and n-channel MOS transistors respectively, with theirdrain terminals coupled together. The source terminal of the rowselection device is connected to the analog ground voltage and thesource terminal of the ISFET is connected to a current source, whichprovides a bias current to the pixel. The output voltage Vout is readout from the source terminal of the ISFET.

FIG. 12H illustrates a 2T pixel, according to one embodiment of thepresent invention. As shown, the ISFET and the row selection device SELare p-channel and n-channel MOS transistors respectively, with theirdrain terminals coupled together. The source terminal of the rowselection device is connected to the analog ground voltage and thesource terminal of the ISFET is connected to a current source, whichprovides a bias current to the pixel. The output voltage Vout is readout from the source terminal of the ISFET. The source terminal of theISFET is connected to the body terminal to eliminate the body effect.

FIGS. 13A to 13D illustrate common source 2T cell configurationsaccording to embodiments of the present invention. In FIGS. 13A and 13B,both the ISFET and the row selection device are n-channel MOStransistors, and in FIGS. 13C and 13D, both the ISFET and the rowselection device are p-channel MOS transistors.

In FIG. 13A, the source terminal of the ISFET is connected to the analogground supply and the drain terminal of the row selection device isconnected to a current source, which provides a bias current to thepixel. The source terminal of the row selection device and the drainterminal of the ISFET are connected together. The output voltage Vout isread out from the drain terminal of the row selection device.

In FIG. 13B, the source terminal of the row selection device isconnected to the analog ground supply and the drain terminal of theISFET is connected to a current source, which provides a bias current tothe pixel. The drain terminal of the row selection device and the sourceterminal of the ISFET are connected together. The output voltage Vout isread out from the drain terminal of the ISFET.

In FIG. 13C, the source terminal of the ISFET is connected to the analogsupply voltage, and the drain terminal of the row selection device isconnected to a current source, which provides a bias current to thepixel. The source terminal of the row selection device and the drainterminal of the ISFET are connected together. The output voltage Vout isread out from the drain terminal of the row selection device.

In FIG. 13D, the source terminal of the row selection device isconnected to the analog supply voltage, and the drain terminal of theISFET is connected to a current source, which provides a bias current tothe pixel. The source terminal of the ISFET and the drain terminal ofthe row selection terminal are connected together. The output voltageVout is read out from the drain terminal of the ISFET.

FIG. 14A shows a 2T pixel array according to one embodiment of thepresent invention. For illustrative purposes, eight 2T pixels are shownarranged into two columns, though the 2T pixel array 1400 could extendto an array of any size of 2T pixels. Each column pitch contains threecolumn lines cb[0], ct[0] and cb[1], The row lines rs[0], rs[1], rs[2]and rs[3], connect to all columns in parallel. A row selection device1401RS and an ISFET 1401IS may form one 2T pixel, with the source of1401IS connected to the drain of 1401RS. The source of 1401RS isconnected to the column line cb[0], and the drain of 1401IS is connectedto the column line ct[0]. The gate of 1401RS is connected to the rowline rs[0). This pixel is mirrored in a pixel comprising 1402IS and1402RS, with drains of 1401IS and 1402IS connected to the column linect[0], and the gate of 1402RS connected to the row line rs[1]. The pixelcomprising 1402IS and 1402RS is mirrored in a pixel comprising 1403ISand 1403RS, with the source of 1402RS and 1403RS connected to the rowline cb[1], and the gate of 1403RS coupled to the row line rs[2]. Thepixel comprising 1403IS and 1403RS is mirrored in a pixel comprising1404IS and 1404RS, with the drains of 1403IS and 1404IS connected to therow line ct[0], the gate of 1404RS coupled to the row line rs[3], andthe source of 1404RS coupled to the column line cb[0]. In the embodimentshown in FIG. 14, each of the IS devices is an ISFET and each of the RSdevices is a row select device.

The right column, including a pixel consisting of 1405RS and 1405IS, apixel consisting of 1406RS and 1406IS, a pixel consisting of 1407RS and1407IS, and a pixel consisting of 1408RS and 1408IS, is coupled tocolumn traces cb[2], ct[1], and cb[3] in substantially the same manneras described above.

FIGS. 14B and 14C show a layout for a 2×2 2T pixel array according to anembodiment of the present invention. The 2×2 2T pixel array may be partof the pixel array 1400. FIG. 14B shows that polysilicon gates for1401RS, 1401IS, 1402RS and 1402IS may be placed on top of a continuousdiffusion layer 1410 and polysilicon gates for 1405RS, 1405IS, 1406RSand 1406IS may be placed on top of a continuous diffusion layer 1412. Inone embodiment, the continuous diffusion layers 1410 and 1412 may runfrom the top of the pixel array to the bottom of the pixel array. Thatis, the diffusion layer may have no discontinuities in the pixel array.

FIG. 14C shows where microwells for ISFETs 1401IS, 1402IS, 1405IS and1406IS may be placed. The microwells may be used to hold analytesolutions that may be analyzed by the ISFETs. As shown in FIG. 14C, inone embodiment, the microwells may each have a hexagonal shape andstacked like a honeycomb. Further, in one embodiment, the contact may beplaced directly on top of the gate structure. That is, the ISFETs mayhave a contact landed on polysilicon gate over thin oxide.

The pixel array 1400 has high density because of continuous diffusion,shared contacts, mirrored pixels, and one ct (column top) line and 2 cb(column bottom) line per physical column. A global bulk contact may beimplemented by using a P+ wafer with P− epitaxy region.

The arrangement of pixel array 1400 provides for high speed operation.Row lines rs[0] and rs[1] are selected together and readout throughcb[0] and cb[1]. This leads to a 4 times faster readout due to twice thenumber of pixels enabled for a single readout and half the parasiticload of a continuous array, allowing each column to settle twice asfast. In an embodiment, the full array is separated into a top half anda bottom half. This leads to another 4 times faster readout time due totwice the number of pixels readout at a time (both out the top and thebottom) and half the parasitic load of a continuous array. Thus, thetotal increase in speed over a single row selected continuous array is16 times.

In an embodiment, both top and bottom halves of the pixel array may beenabled at the same time during readout. This can allow a multiplexingof readout between the top half and the bottom half. For example, onehalf can be doing a “wash” (e.g., flushing out reactants from the wellsover the pixel devices) and the other half can be performing thereadout. Once the other half is read, the readout for the two halves isswitched.

In an embodiment, a 2T pixel design can incorporate twochemically-sensitive transistors (e.g., ISFETs) rather than onechemically-sensitive transistor and one row select device as describedwith respect to FIGS. 11-14. Both chemically-sensitive transistors, orISFETs, can be NMOS or PMOS device and configured in a source followeror common source readout mode. Possible uses of such a 2T pixel may bewhere the first chemically-sensitive transistor has a differentsensitivity to a particular analyte to that of the secondchemically-sensitive transistor, allowing a local and in-pixeldifferential measurement to be made. Alternatively, bothchemically-sensitive transistors may have the same sensitivity to aparticular analyte, allowing a local and in-pixel average measurement tobe made. These are among two examples of potential uses for thisembodiment, and based on the description herein, a person of ordinaryskill in the art will recognize other uses for the 2T pixel design thatincorporate two chemically-sensitive transistors (e.g., ISFETs).

In one embodiment, a column circuit allows column lines to be swapped toa sampling circuit such that either source-side or drain-side rowselection can be made in either source follower mode or common sourcemode.

Capacitive Charge Puma

One or more charge pumps may be used to amplify the output voltage froma chemically-sensitive pixel that comprises one or more transistors,such as those described above.

FIG. 15 shows a capacitive charge pump with a two times voltage gainaccording to one embodiment of the present invention. A charge pump 1500may comprise φ1 switches 1501, 1502, 1503 and 1504, φ2 switches 1505 and1506, and capacitors 1507 and 1508. Vref1 and Vref2 are set to obtainthe desired DC offset of the output signal, and both are chosen to avoidsaturation of the output during the boost phase. The operation of thecharge pump may be controlled by timing signals, which may be providedby a timing circuit.

At time t0, all switches are off.

At time t1, φ1 switches 1501, 1502, 1503 and 1504 are turned on. Thetrack phase may start. An input voltage Vin, which may be from an ionsensitive pixel, may start to charge capacitors 1507 and 1508.

At time t2, φ1 switches 1501, 1502, 1503 and 1504 are turned off, andcapacitors 1507 and 1508 are charged to Vin−Vref1.

At time t3, φ2 switches 1505 and 1506 are turned on, while φ1 switches1501, 1502, 1503 and 1504 remain off. The boost phase may start. Thecapacitor 1507 may start to discharge through the capacitor 1508. Sincethe capacitors are in parallel during the track phase and in seriesduring the boost phase, and the total capacitance is halved during theboost phase while the total charge remains fixed, the voltage over thetotal capacitance must double, making Vout approximately two times Vin.

A source follower SF may be used to decouple the gain circuit from thefollowing stage.

The charge pump 1500 may provide a two times gain without a noisyamplifier to provide a virtual ground.

FIG. 16 shows a charge pump according to an embodiment of the presentinvention.

At time t0, all switches are off.

At time t1, φ1 switches 1501, 1502, 1503, 1504, 1601 and 1602 are turnedon. The track phase may start. An input voltage Vin, which may be froman ion sensitive pixel, may start to charge capacitors 1507, 1508 and1604.

At time t2, φ1 switches 1501, 1502, 1503, 1504, 1601 and 1602 are turnedoff, and capacitors 1507, 1508 and 1604 are charged to Vin−Vref1.

At time t3, φ2 switches 1505 and 1603 are turned on, while φ1 switches1501, 1502, 1503, 1504, 1601 and 1602 remain off. The boost phase maystart. The capacitor 1507 may start to discharge through the capacitors1508 and 1604, and the capacitor 1508 may start to discharge through thecapacitor 1604. Since the capacitors are in parallel during the trackphase and in series during the boost phase, and the total capacitance isdivided by three during the boost phase while the total charge remainsfixed, the voltage over the total capacitance must triple, making Voutapproximately three times Vin.

FIG. 17 shows an embodiment of a charge pump according to an embodimentof the present invention. Two charge pumps 1500 shown in FIG. 15 areconnected in series, enabling gain pipelining and amplifying inputvoltage Vin by a factor of four.

Additional series charge pumps can be added to increase the gainfurther. In a multi-stage charge pump, the capacitor values do not haveto be the same size from stage to stage. It can be observed that thetotal area consumed by capacitors increases with the square of the gain.Although this feature may, in some cases, be undesirable with respect toarea usage, power consumption, and throughput, the charge pump can beused without these penalties when the total noise produced by the ionsensitive pixel and associated fluidic noise is larger than the chargepump KT/C noise when a reasonable capacitor size is used.

FIG. 18 shows an embodiment of a charge pump according to an embodimentof the present invention. A feedback path including a source followerSFP and a switch φpfb is added to the charge pump 1500, feeding theoutput Vout back to the input of the charge pump.

At time t0, all switches are off.

At time t1, a switch φpsp is on, providing an input voltage Vin to theinput of the charge pump 1500.

From time t2 to time t5, the charge pump 1500 operates to push theoutput voltage Vout to 2(Vin−Vref1), as described before with referenceto FIG. 15.

From time t6 to t7, the switch φfb is on, feeding the output voltage2(Vin−Vref1). back to the input of the charge pump 1500, and the firstcycle ends.

During the second cycle, the charge pump 1500 amplifies the outputvoltage by 2(2(Vin−Vref1)). The process repeats, with the output beingamplified during each cycle.

CCD-Based Multi-Transistor Active Pixel Sensor Array

An ion sensitive MOS electrode is charge coupled to adjacent electrodesto facilitate both confinement and isolation of carriers. Measurementsof ion concentration are made by discrete charge packets produced ateach pixel and confined by potential barriers and wells. The ionsensitive electrode can act as either a barrier level or as a potentialwell. Working in the charge domain provides several benefits, includingbut not limited to: 1) increased signal level and improved signal tonoise through the accumulation of multiple charge packets within eachpixel, 2) better threshold matching of the MOS sensing and referencestructures, 3) reduction in flicker noise, and 4) global-snap shotoperation.

A floating electrode is used to detect ions in close proximity to theelectrode. The electrode is charge coupled to other electrodes and toother transistors to form a pixel that can be placed into an array foraddressable readout. It is possible to obtain gain by accumulatingcharge into another electrode or onto a floating diffusion (FD) node ordirectly onto the column line. It is desirable to achieve both areduction in pixel size as well as increase in signal level. To reducepixel size, ancillary transistors may be eliminated and a charge storagenode with certain activation and deactivation sequences may be used.

The ion sensitive (IS) accumulation pixel contains some of the followingconcepts:

-   -   1. Electrodes are charge coupled to the IS electrode;    -   2. A source of carriers (electrons or holes) for charge packets;    -   3. A reference electrode to act as a barrier or a well for the        charge packets;    -   4. A floating diffusion node for charge to voltage conversion;    -   5. Ancillary transistors to provide buffering and isolation for        addressable readout; and    -   6. Sequences to eliminate some or all ancillary transistors        depending on the application.

The basic IS accumulation pixel is shown in FIG. 19. Charge accumulationcan occur either locally at the time of readout or globally during aseparate integration time. The embodiment shown in FIG. 19 is a threetransistor three electrode (3T3E) pixel. The three transistors include areset transistor RT, a source follower 1901 and a row selectiontransistor RS, and the three electrodes include an electrode VS, anelectrode VR, and an ion sensitive electrode 1902. The pixel alsoincludes a transfer gate TX. It is also possible to configure the ISaccumulation pixel with additional elements to allow simultaneousaccumulation and readout. This can be done, for example, by adding 2more electrodes to pipeline the process. In the basic configuration,charge is accumulated onto the floating diffusion node that is connectedto the source of the reset (RT) control gate. In a rolling shutteroperation, the floating diffusion (FD) is reset to CD=VDD. The row isthen selected and readout through the source follower enabled by rowselection (RS). Next, charge is accumulated onto the FD node whichdischarged the parasitic capacitor. A second sample is then taken. Thedifference between the samples represents the ion concentration. Thesamples are correlated and taken relatively quickly in time. Therefore,the thermal noise of the readout circuit is eliminated and the 1/f noiseis reduced. To operate in a global shutter mode, all FD nodes aresimultaneously reset to VDD. Then charge is accumulated on each isolatedFD node. After accumulation, each row is selected by enabling the RSgate. The signal value is readout on the column line with a load on thesource follower. Next the pixel is reset and sampled again. Thedifference between the samples represents the ion concentration. The 1/fnoise is reduced through the double sampling. However, the thermal resetnoise is not eliminated because the reset value is uncorrelated in time.The thermal noise can be reduced by half the power by following thereset operation with a subthreshold reset before sampling. In general,the thermal noise is low compared to the signal due to the chargeaccumulation. A correlated reset scheme with global shutter is availablein other configurations.

The basic charge accumulation scheme is shown in FIG. 20 using thesurface potential diagrams. Only the electrodes are shown since thetransistors are only used for readout. In each of these sequences,increasing potential is pointing down as is conventional to showpotential wells containing electrons. Four cycles of charge accumulationare shown in FIG. 20 A-Q. First, all charge is removed from the channelunder the IS electrode and the channels are fully depleted using a highpotential on FD (A). Next, the TX gate transitions to a low potentialwhich creates the confinement barrier (B). A fill and spill operation isused to produce a charge packet proportional to the ion concentration atthe IS electrode (C-D). In the next cycle, this charge packet istransferred to the FD node which discharges due to the electrons. Thediagram shows electrons accumulating on the FD node, but the voltage isactually decreasing. After many cycles, as shown in FIG. 20 E-Q, thesignal to noise ratio is improved and the signal can be read out withgain. Hundreds to millions of cycles can be used to amplify the signal.

In alternative embodiments, the order of electrodes may be switched,and/or the IS electrode may be used as the barrier rather than the well.Transistors may be added to this accumulation line to enable a largearray of pixels. The ancillary transistors are used to increase speed.However, it should be noted that no transistors are necessary to enablea full pixel array of the accumulation line. Instead, an array can bepartitioned such that no transistors are needed. In an embodiment, theFD nodes are connected to the column line. Before a pixel is read out,the column line is reset to VDD. Then a row is selected by accumulatingcharge for that row directly onto the column line. After many cycles,the column discharges to a value directly proportional to the ionconcentration. Since the capacitance of the column line depends on thetotal number of rows, the amount of accumulation required, depends onthe number of rows. The array can be partitioned into sub arrays to maketiming scalable. For example, every 100 rows can contain a local sourcefollower buffer that is then connected to a global array. Thishierarchical approach can be used in general with all readout schemes tomake massive arrays of pixels with fast readout.

Due to the thermal activity of carriers, charge packets cannot begenerated without noise. Each fill and spill operation produces chargeerror proportional to KTC (thermal noise in the floating diffusioncapacitor), where C is equal to Cox times the area of the ion sensitiveelectrode. During the fill operation charge can flow freely between thesource of electrons and the confinement well. However, during the spilloperation, the device enters the subthreshold mode and carriers move bydiffusion, mainly in only one direction, which results in half of thethermal noise of a resistive channel. The total noise in electrons foreach charge packet is therefore sqrt(KTC/2)/q where q represents thecharge of one electron in coulombs (1.6×10e−19). The signal in electronsis equal to VC/q. The signal to noise ratio after n cycles is equal toV*sqrt(2nC/KT). Note that the signal to noise ratio improves by thesquare root of the number of cycles of accumulation. For small signallevels, the amount of accumulation will be limited to the thresholdmismatch between the VR reference electrode and the ion sensitiveelectrode. Since there is a reference electrode in every pixel and theelectrodes are charge coupled, the relative threshold mismatch betweeneach pair of electrodes is small. Assuming, this difference is about 1mV, over 1000 accumulation cycles should be feasible, thereby improvingthe signal to noise by more than 30 times. By way of example, if thesignal is 1 mV and the electrode area is 1 square micron withCox=5fF/um^2, the signal to noise ratio after 1000 cycles is 50 to 1.Since the signal level then reaches 1V, it is expected that no othernoise source is relevant. For clarity, the dominant noise is simply thecharge packet thermal noise which is well known.

FIGS. 21 and 22 show the IS accumulation pixel with only 2 transistors.The selection transistor is eliminated by using a deactivation sequenceafter a row is read out. To deactivate, the FD node is discharged, whichreduces the potential of the FD node and disables the source followerfor that row. The surface potential diagrams for the pixel of FIG. 22are shown in FIG. 23.

FIG. 24 shows the IS accumulation pixel with 2 transistors and 4electrodes. This pixel produces the fill and spill charge packets andreadout all at the same FD node. The 4th electrode allows global shutteroperation and correlated double sampling. For faster readout, singlesampling can be used if charge accumulation sufficiently reduces the 1/fnoise contribution. FIG. 25 shows the surface potential diagrams for thebasic operation of the pixel of FIG. 24.

FIG. 26 shows an IS accumulation pixel with 1 transistor and 3electrodes. The channel can be depleted and supplied from the same node.This pixel depends on charge coupling, and signal range is lower thansignal range for the other pixels.

Several design permutations are available depending on the desired modeof operation. The CCD channels are surface mode and are built instandard CMOS technology preferably below 0.13 um. Extra implants can beadded to avoid surface trapping and other defects. A channel stop andchannel can be formed from donor and acceptor impurity implants. Thechannel can be made of multiple implants to produce a potential profileoptimal for the mode of operation.

FIG. 27 shows an embodiment of a three transistor (3T) active pixelsensor. The three transistors are a reset transistor 2701, a sourcefollower 2702 and a row selection switch 2703. The reset transistor 2701has a gate controlled by a reset signal RST, a source coupled to thefloating diffusion (FD) of a pixel, and a drain connected to a fixedvoltage. The source follower 2702 has its gate connected to the sourceof the reset transistor 2701, and its drain connected to a fixedvoltage. A row selection transistor 2703 has its gate connected to a rowline, its drain connected to a fixed voltage and its source connected toa column. Other electrodes interacting with the pixel includes atransfer gate TG, an ion selective electrode ISE, an input control gateICG, and an input diffusion ID. These three elements form charge coupledelectrodes that are operated in an identical way to VS, VR, and TX inFIG. 19.

FIG. 28 shows an alternate embodiment of a 3T active pixel sensor. Thedifference between the sensor in FIG. 28 and the sensor shown in FIG. 27is that the sensor 2800 has a second input control gate ICG2, whichallows more control over the potential barrier near the ion-sensitiveelectrode.

FIG. 29 shows an embodiment of a 3T active pixel sensor with a sampleand hold circuit, which may be used to eliminate signal variations. Asshown, the gate of the row selection transistor 2703 is controlled by aRowSelm signal provided by a row selection shift register. The source ofthe row selection transistor 2703 is coupled to a current sink ISink2902 and a column buffer 2903. The current sink ISink 2902 may be biasedby a voltage VB1 and the column buffer, which may be an amplifier, maybe biased by a voltage VB2.

The sample and hold circuit 2901 may include a switch SH, a switch CAL,a capacitor Csh, and an amplifier Amp. The switch SH's input is coupledto the output of the column buffer 2903, and its output is coupled to avoltage VREF through the switch CAL, the upper part of the capacitorCsh, and the input of the amplifier Amp. The amplifier is biased by avoltage VB2. The output of the amplifier is coupled to a switch 2904controlled by a signal ColSeln from a column selection shift register.The output of the switch 2904 is buffered by an output buffer 2905before reaching the output terminal Vout. The output buffer is biased bya voltage VB3.

FIG. 30 shows an embodiment of a 3T active pixel sensor with acorrelated double sampling circuit. The most significant differencebetween the sensor in FIG. 30 and that in FIG. 29 is that the formeruses a correlated double sampling circuit 3001 to measure the signalfrom the column buffer 2903. An amplifier in the correlated doublesampling circuit 3001 receives at its first input the output of thecolumn buffer 2903 via a switch SH, and a capacitor Cin. The amplifierreceives a reference voltage VREF at its second input, and is biased bythe voltage VB2. A reset switch RST and a capacitor Cf are coupled inparallel with the amplifier.

FIG. 31 shows an embodiment of a 2.5T active pixel sensor used for afour pixel array. Each of the pixels has its own transfer transistorTX1, TX2, TX3 and TX4 and its own reset transistor. The drain of eachtransfer transistor is coupled to the source of the reset transistor inthe same pixel, and the source of each transfer transistor is coupled tothe gate of the source follower.

FIG. 32 shows an embodiment of a 1.75T active pixel sensor for a fourpixel array. Each of the pixels has its own transfer transistor. Thesource of each transfer transistor is coupled to the floating diffusionof the same pixel, and the drain of each transfer transistor is coupledto the drain of the reset transistor RST of the sensor.

Several embodiments of the present invention are specificallyillustrated and described herein. However, it will be appreciated thatmodifications and variations of the present invention are covered by theabove teachings. In other instances, well-known operations, componentsand circuits have not been described in detail so as not to obscure theembodiments. It can be appreciated that the specific structural andfunctional details disclosed herein may be representative and do notnecessarily limit the scope of the embodiments. For example, someembodiments are described with an NMOS. A skilled artisan wouldappreciate that a PMOS may be used as well.

Those skilled in the art may appreciate from the foregoing descriptionthat the present invention may be implemented in a variety of forms, andthat the various embodiments may be implemented alone or in combination.Therefore, while the embodiments of the present invention have beendescribed in connection with particular examples thereof, the true scopeof the embodiments and/or methods of the present invention should not beso limited since other modifications will become apparent to the skilledpractitioner upon a study of the drawings, specification, and followingclaims.

Various embodiments may be implemented using hardware elements, softwareelements, or a combination of both. Examples of hardware elements mayinclude processors, microprocessors, circuits, circuit elements (e.g.,transistors, resistors, capacitors, inductors, and so forth), integratedcircuits, application specific integrated circuits (ASIC), programmablelogic devices (PLD), digital signal processors (DSP), field programmablegate array (FPGA), logic gates, registers, semiconductor device, chips,microchips, chip sets, and so forth. Examples of software may includesoftware components, programs, applications, computer programs,application programs, system programs, machine programs, operatingsystem software, middleware, firmware, software modules, routines,subroutines, functions, methods, procedures, software interfaces,application program interfaces (API), instruction sets, computing code,computer code, code segments, computer code segments, words, values,symbols, or any combination thereof. Determining whether an embodimentis implemented using hardware elements and/or software elements may varyin accordance with any number of factors, such as desired computationalrate, power levels, heat tolerances, processing cycle budget, input datarates, output data rates, memory resources, data bus speeds and otherdesign or performance constraints.

Some embodiments may be implemented, for example, using acomputer-readable medium or article which may store an instruction or aset of instructions that, if executed by a machine, may cause themachine to perform a method and/or operations in accordance with theembodiments. Such a machine may include, for example, any suitableprocessing platform, computing platform, computing device, processingdevice, computing system, processing system, computer, processor, or thelike, and may be implemented using any suitable combination of hardwareand/or software. The computer-readable medium or article may include,for example, any suitable type of memory unit, memory device, memoryarticle, memory medium, storage device, storage article, storage mediumand/or storage unit, for example, memory, removable or non-removablemedia, erasable or non-erasable media, writeable or re-writeable media,digital or analog media, hard disk, floppy disk, Compact Disc Read OnlyMemory (CD-ROM), Compact Disc Recordable (CD-R), Compact DiscRewriteable (CD-RW), optical disk, magnetic media, magneto-opticalmedia, removable memory cards or disks, various types of DigitalVersatile Disc (DVD), a tape, a cassette, or the like. The instructionsmay include any suitable type of code, such as source code, compiledcode, interpreted code, executable code, static code, dynamic code,encrypted code, and the like, implemented using any suitable high-level,low-level, object-oriented, visual, compiled and/or interpretedprogramming language.

What is claimed is:
 1. An ion sensitive (IS) accumulation pixel circuitto detect a chemical or a bio-chemical reaction, comprising: a readoutcircuit; an IS electrode; at least two electrodes charge coupled to theIS electrode; and a floating diffusion node configured to convert anaccumulated charge from the chemical or the bio-chemical reaction to acorresponding voltage, wherein the floating diffusion node is coupled tothe readout circuit.
 2. The IS accumulation pixel circuit of claim 1,wherein one of the at least two electrodes is a reference electrodeconfigured to act as a barrier for charge packets.
 3. The ISaccumulation pixel circuit of claim 1, wherein one of the at least twoelectrodes is a reference electrode configured to act as a well forcharge packets.
 4. The IS accumulation pixel circuit of claim 1, whereinthe readout circuit comprises one and only one transistor with a sourcecoupled to both the floating diffusion node and a first column line anda drain coupled to a second column line.
 5. The IS accumulation pixelcircuit of claim 4, wherein a gate of the one and only one transistor iscoupled to a second diffusion node in the IS accumulation pixel circuit.6. The IS accumulation pixel circuit of claim 1, wherein the readoutcircuit comprises two and only two transistors, and wherein the twotransistors comprise a reset transistor and a source followertransistor.
 7. The IS accumulation pixel circuit of claim 6, wherein asource of the reset transistor is coupled to the floating diffusion nodeand a drain of the reset transistor is coupled to a second column line.8. The IS accumulation pixel circuit of claim 7, wherein the sourcefollower transistor has a gate coupled to the source of the resettransistor, and a drain coupled to the second column line.
 9. The ISaccumulation pixel circuit of claim 6, wherein the reset transistor hasa source coupled to a second floating diffusion node, and a draincoupled to a second column line.
 10. The IS accumulation pixel circuitof claim 9, wherein the source follower transistor has a source coupledto the floating diffusion node and a first column line, and a draincoupled to the first column line.
 11. The IS accumulation pixel circuitof claim 6, wherein the reset transistor has a source coupled to thefloating diffusion node, and a drain coupled a second column line. 12.The IS accumulation pixel circuit of claim 11, wherein the sourcefollower transistor has a gate coupled to the source of the resettransistor, a drain coupled to the second column line and a sourcecoupled to a first column line.
 13. The IS accumulation pixel circuit ofclaim 1, wherein the readout circuit comprises a reset transistor, asource follower transistor and a row selection transistor.
 14. The ISaccumulation pixel circuit of claim 13, wherein the reset transistor hasa source coupled to the floating diffusion node, and a drain coupled toa second column line.
 15. The IS accumulation pixel circuit of claim 13,wherein the source follower transistor has a gate coupled to a source ofthe reset transistor, and a drain coupled to a second column line. 16.The IS accumulation pixel circuit of claim 13, wherein the row selectiontransistor has a drain coupled to a source of the source followertransistor, and a source coupled to a first column line.
 17. The ISaccumulation pixel circuit of claim 13, wherein a source of the rowselection transistor is coupled to a sample and hold circuit via abuffer.
 18. The IS accumulation pixel circuit of claim 13, wherein asource of the row selection transistor is coupled to a correlated doublesampling circuit via a buffer.
 19. A pixel array to detect a chemical ora bio-chemical reaction, comprising at least two IS accumulation pixelcircuits, wherein each IS accumulation pixel circuit further comprises:a readout circuit; an IS electrode; at least two electrodes chargecoupled to the IS electrode; and a floating diffusion node configured toconvert an accumulated charge from the chemical or the bio-chemicalreaction to a corresponding voltage; wherein the floating diffusion nodeis coupled to the readout circuit.
 20. The pixel array of claim 19,wherein the readout circuit comprises one and only one transistor with asource coupled to both the floating diffusion node and a first columnline and a drain coupled to a second column line.
 21. The pixel array ofclaim 19, wherein the readout circuit comprises two and only twotransistors, and wherein the two transistors comprise a reset transistorand a source follower transistor
 22. The pixel array of claim 19,wherein the readout circuit comprises a reset transistor, a sourcefollower transistor and a row selection transistor.
 23. An ion sensitive(IS) accumulation pixel circuit to detect a chemical or a bio-chemicalreaction, comprising: an IS electrode; at least two electrodes chargecoupled to the IS electrode; a floating diffusion node configured toconvert an accumulated charge from the chemical or the bio-chemicalreaction to a corresponding voltage; a reset transistor, having a sourcecoupled to the floating diffusion node and a drain coupled to a fixedvoltage; and a transfer transistor, having a drain coupled to the sourceof the reset transistor.
 24. A pixel array to detect a chemical or abio-chemical reaction, comprising: at least two ion sensitiveaccumulation pixel circuits, each comprising: an IS electrode; at leasttwo electrodes charge coupled to the IS electrode; a floating diffusionnode configured to convert an accumulated charge from the chemical orthe bio-chemical reaction to a corresponding voltage; a resettransistor, having a source coupled to the floating diffusion node and adrain coupled to a fixed voltage; and a transfer transistor, having adrain coupled to the source of the reset transistor; and a readoutcircuit, comprising: a source follower transistor with a gate coupled tosources of the at least two ion sensitive accumulation pixel circuits;and a row selection transistor with a gate coupled to a row line, adrain coupled to a source of the source follower transistor, and asource coupled to a column line.
 25. An ion sensitive (IS) accumulationpixel circuit, comprising: an IS electrode; at least two electrodescharge coupled to the IS electrode; a floating diffusion node configuredto convert an accumulated charge from the chemical or the bio-chemicalreaction to a corresponding voltage; and a transfer transistor, having adrain coupled to the floating diffusion node.
 26. A pixel array,comprising: at least two ion sensitive accumulation pixel circuits, eachcomprising: an IS electrode; at least two electrodes charge coupled tothe IS electrode; a floating diffusion node configured to convert anaccumulated charge from the chemical or the bio-chemical reaction to acorresponding voltage; and a transfer transistor, having a drain coupledto the floating diffusion node; and a readout circuit, comprising: areset transistor with a source coupled to the drain of the transfertransistor; a source follower transistor with a gate coupled to thedrain of the transfer transistor; and a row selection transistor with agate coupled to a row line, a drain coupled to the source of the sourcefollower transistor, and a source coupled to a column line.